The hypothesis that reactive oxygen species (ROS) modification of DNA is involved in the development of autoantibodies in systemic lupus erythematosus (SLE) is supported by the enhanced reactivity of anti-DNA antibodies to ROS-denatured DNA. We studied the efficacy of vitamin E against both oxidative DNA damage and autoantibody production in SLE. Urinary 8-hydroxydeoxyguanosine (8-OHdG), an indicator of oxidative DNA damage, and the anti-double-stranded DNA (anti-ds DNA) antibody, a predictor of disease activity, were assayed twice, first during the season with the most intense sunlight and then later in the year. Twelve women among 36 outpatients received vitamin E (150 to 300 mg/day) together with prednisolone (PSL). No significant age or daily dose of PSL differences were evident between patient groups. Urinary 8-OHdG in the PSL with vitamin E group (15.0 +/- 10.2 ng/mg during the period of intense sunlight and 11.7 +/- 8.7 ng/mg during the remainder of the year) did not differ significantly from that in the PSL without vitamin E group (20.0 +/- 23.2 and 11.0 +/- 5.9 ng/mg, at these respective times), but the anti-ds DNA antibody titer in the PSL with vitamin E group (17.9 +/- 20.3 IU/l during the period of intense sunlight and 16.3 +/- 19.4 IU/l during the remainder of the year) was significantly lower than that in the PSL without vitamin E group for both sunlight-defined periods (66.3 +/- 76.8 and 55.8 +/- 59.0 IU/l, at these respective times; P < 0.05). The present study suggests that vitamin E can suppress autoantibody production via a mechanism independent of antioxidant activity.